A major objective of the proposed research is to elucidate mechanisms by which drugs alter functions of the thermoregulatory system by simultaneous quantitative measurement at a variety of environmental temperatures of drug-induced changes in body temperature of restrained squirrel monkeys and of changes in thermoregulatory effector activities, including metabolic rate, evaporative heat loss and cutaneous blood flow, which cause or accompany the alterations in body temperature. Agents to be studied include lysergic acid diethylamide, tetrahydrocannabinol or marihuana, morphine and histamine. The remaining studies will involve automatic recording of deep body temperature in unrestrained cats provided with chronically implanted thermocouples, iv catheters and/or intracerebral cannulas or guide tubes for injections into the ventricular system or directly into the hypothalamus or other cerebral loci. A second objective is to clarify the role of prostaglandins as intermediates in the production of fever by pyrogens. Release of prostaglandins into CSF or from brain slices by leukocytic pyrogen, effects of intracerebral administration of prostaglandin precursors on body temperature and a possible role of cyclic AMP in prostaglandin-induced fever will be investigated. The final objective is to continue investigations on the mechanism of action of antipyretic agents with particular attention being given to interactions between antipyretics and the release and activity of leukocytic pyrogen and on agents with possibly novel mechanisms of antipyretic action. Indomethacin, phenylbutazone and other pyrazolone derivatives, para-aminophenol derivatives, corticosteroids and N- phenylbarbital are among the agents to be examined.